Transcript Document

Pregnancy and HIV Acquisition
Nelly Mugo
Kenyatta National Hospital/
University of Washington
Hormonal Contraception: the Role of Fertility Choice in HIV
Prevention
AIDS 2012, Global Village, Session Room 1
Thursday 26th July
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Outline
Fertility rates
Association of pregnancy & HIV
»Biological plausibility
HIV Incidence in pregnancy & breast feeding
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Back ground
More than 50% of women with HIV1infection worldwide are women (UNAIDS
2010 Report)
 In sub-Saharan Africa, fertility rates are high
• Majority (42%) of new HIV infections
occur within reproductive years age 1524 years
• United Nation's Millennium Development
Goals 4 and 5 aim to reduce child
deaths and improve maternal health.
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Peak HIV prevalence among women
age: 24-34 years
25
Malawi
20
Women
50
15
Swaziland
45
10
43
40
38
35
5
36
30
0
15-19
20-24
25-29
30-34
35-39
40-44
45-49
12
6
19
10
Men
0
12
10
9
6
5
Women
Men
16
15
Uganda
10
8
Women
25
20
14
HIV Prev
HIV prevalence (%)
Men
2
15-19
1.5
15-17
3
18-19
20-24
20-22
23-24
4
2
0
15-19 20-24 25-34 30-34 35-39 40-44 45-49 50-54 55-59
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Washington D.C., USA, 22-27 July 2012
High Fertility Rates in Sub Saharan Africa
WHO Report
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Does Pregnancy Increase HIV-1 Risk?

Physiological changes of pregnancy
High levels of progesterone could induce systemic
and immunologic changes
 Unprotected sex in efforts to conceive and continued
during pregnancy
make pregnant women vulnerable to HIV-1
infection
Sheffield JS., Reprod Sci. 2009
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Washington D.C., USA, 22-27 July 2012
Does Pregnancy Increase HIV-1 Risk?
Male-to-female HIV-1 transmission
(increased susceptibility of HIV neg pregnant woman)
HIV-1
HIV-pos male
HIV-neg pregnant
female
Female-to-male HIV-1 transmission
(increased infectiousness of HIV-pos pregnant woman)
HIV-1
HIV-neg male
HIV-pos pregnant
female
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HIV incidence during pregnancy /and or
breastfeeding
Author, year
Location
Population
HIV Incidence/100 per
years
Keating MA,
PloSOne 2012
Malawi
ANC
4.0
Mugo, NR, AIDS
2011
East & South Africa
Serodiscordant
couples
7.4
Moodley JID 2011
Kwa Zulu Natal,
South Africa
ANC
2.5
Humprey JH, BMJ
2010
Zimbabwe
ANC
3.5
Kinuthia J, Curr HIV
Res 2010
Kenya
ANC
6.8
Morrison C, AIDS
2007
Uganda Zimbabwe
Family Planning 1.6
clinics
Gray RH, Lancet
2005
Uganda
Sero-discordant 2.2
couples
Mbidzo MT, Centr
Afri J Med 2001
Zimbabwe
ANC
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4.8
Washington D.C., USA, 22-27 July 2012
Pregnancy and HIV-1 Risk: Summary
Male-to-female HIV-1 Transmission


Observational studies demonstrate increased HIV incidence in pregnancy
and early post partum (2.6 - 4.4%)*
Only 3 prospective studies have examined in detail the effect of
pregnancy on women’s HIV risk with contradictory findings:
 Uganda: IRR 2.16
 Uganda/ Zimbabwe: HR 0.6
 East/South Africa: 2.3
Female-to-male HIV-1 Transmission


The effect of pregnancy on HIV transmission risk is only hypothesized
through indirect studies of HIV infectiousness
e.g., increased genital HIV-1 shedding (Clemetson D, JAMA1993)
One study has explored pregnancy as a direct risk factor for F-to-M HIV
transmission
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Risk of Neonatal Infection
• Acute HIV infection increases risk for mother to
child transmission
– 26% (95% CI 22-30%)
A proportion of 15,000 of 57,000 neonatal
infections
Johnson LF, J Acquir Immun Defic Syndr. 2012
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Washington D.C., USA, 22-27 July 2012
SUMMARY: Pregnancy Incidence ,
HSV/HIV Transmission Study
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Washington D.C., USA, 22-27 July 2012
14 Sites for Partners in Prevention
HSV/HIV Transmission Study
Nairobi, Thika
Eldoret, Kisumu
Kenya (4)
Lusaka, Kitwe,
Ndola, Zambia (3)
Kampala, Uganda
Moshi, Tanzania
Gaborone,
Botswana
Kigali, Rwanda
Soweto, Orange
Farm, Cape Town
(Gugulethu)
South Africa (3)
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Study Population & HIV-1 Incidence
3321 eligible couples
1085 (33%)
male HIV-pos
female HIV-neg
2236 (67%)
female HIV-pos
male HIV-neg
Female-to-male transmission
Male-to-female transmission
61 HIV-1
seroconversion events
58 *linked* HIV-1
seroconversion events
HIV-1 incidence:
3.6 per 100 person-years
HIV-1 incidence:
1.7 per 100 person-years
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Washington D.C., USA, 22-27 July 2012
Increased risk for HIV-1 transmission
risk in pregnancy
HIV-1
events
HIV-1
incidence¹
Un-adjusted
HR (95% CI)
²Adjusted HR
(95% CI)
All seroconversions
61
3.6
Not during pregnancy
44
3.0
1.0
1.0
During pregnancy
17
7.4
2.3 (1.3-4)
p=0.009
1.6 (0.9-2.9)
p=0.12
All seroconversion
58
1.7
Not during pregnancy
46
1.6
1.0
1.0
During pregnancy
12
3.5
2.2 (1.2-4.1)
p=0.02
2.3 (1.2-4.4)³
p=0.02
Male-female
Linked female-male
¹per 100 person-years
²Adjusted for age, unprotected sex and contraceptive use;
³male circumcision, plasma HIV VL, CD4 cell count, outside partners, ART use, sex acts
did not confound this risk estimate
www.aids2012.org
Mugo et al AIDS 2011
Washington D.C., USA, 22-27 July 2012
Increased Risk for HIV Transmission and
Acquisition in Pregnancy
Approximately 2-fold increased HIV-1 risk during pregnancy for both HIV-1
uninfected pregnant woman & HIV-1 uninfected male partners of HIV-1
infected pregnant woman
 male-to-female unadjusted HR 2.3
 95% CI (1.3 - 4) p=0.009
 female-to-male HIV transmission unadjusted HR 2.2
 95% CI (1.1 - 4.1) p= 0.02
Mugo et al AIDS 2011
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Pregnancy and Male-to-Female
HIV-1 Transmission
 The effect of pregnancy on male-to-female appeared to be
largely explained by behavioural factors, becoming attenuated
and not statistically significant in adjusted analysis
 unadjusted HR 2.3 , 95% CI 1.3-4.0, p=0.009
 adjusted HR: 1.6, 95% CI 0.9-2.9, p=0.12
 Pregnancy & HIV-1 infection both require unprotected sex
 Socio-cultural pressure & desire for pregnancy may outweigh motivation
to prevent HIV-1 infection among couples
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Washington D.C., USA, 22-27 July 2012
Pregnancy and Female-to-Male
HIV-1 Transmission
 In contrast, female-to-male increased transmission risk
is not fully attributable to confounding factors
– Unadjusted HR 2.2, 95% CI 1.2-4.4, p=0.02
– Adjusted HR 2.3, 95% CI 1.2-4.4, p=0.02
 May be due to increased HIV-1 genital shedding ( surrogate for
infectiousness ) in pregnancy (Clemetson et al JAMA 1993)
This has been the first study to demonstrate an increase in
female-to-male HIV-1 risk with pregnancy.
www.aids2012.org
Washington D.C., USA, 22-27 July 2012
Discussion
 Women spend a substantial number of years pregnant in sub-
Saharan Africa (fertility @ 4 pregnancies per lifetime)
 Pregnancy exposure is an important risk factor for HIV
infection (mother, baby, partner)
 Calls for repeat HIV testing in 3rd Trimester and possibly post
partum where it is not yet routine
 Male partner prevention is often not factored into perinatal HIV-1
strategies
 Opportunity for couples counseling and reduction both
perinatal and sexual transmission of HIV
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Washington D.C., USA, 22-27 July 2012
Acknowledgement
FHI 360
IAS conference organizers
HSV/HIV Transmission study teams
All of you
All pregnant women-lets work towards improving
maternal and neonatal health
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Washington D.C., USA, 22-27 July 2012
Thank you
Asante Sana
www.aids2012.org
Washington D.C., USA, 22-27 July 2012